Discovery of a new Bcl-2 inhibitor through synthesis, anticancer activity, docking and MD simulations

Abstract

A database of 300 compounds was virtually screened and docked against Bcl-2 protein; the stability of the best-formed complex was evaluated through Molecular dynamics, the top ten compounds with the best in-silico complexation affinities were synthesized, and their In-vitro cytotoxic activity was examined. Thiazolidinone (4e) and isoxazoline (4a-d) were evaluated in-silico. For further evaluation and examination, we designed and synthesized from naturally occurring (R)-carvone and characterized it via spectroscopic analysis, as well as tested for their anticancer activities towards human cancer cell lines such as HT-1080 (fibrosarcome cancer), MCF-7 and MDA-MB-231 (breast cancer) and A-549 (lung cancer) by using MTT method with Doxorubicin as standard drug. Among them, compound 4d showed the most promising anticancer activity against HT-1080, A-549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 15.59 ± 3.21 µM; 18.32 ± 2.73 µM; 17.28 ± 0.33 µM and 19.27 ± 2.73 µM respectively.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cancer
• bcl-2 protein
• isoxazoline-thiazolidinone
• molecular docking and dynamic
• virtual screening
• cytotoxic activity

Availability of data and materials

All data generated or analyzed during this study are included in this published article. Any further datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.